Prothrombin in normal human cerebrospinal fluid originates from the blood

Area of Science:

• Neuroscience
• Biochemistry
• Immunology

Background:

• Prothrombin, essential for blood coagulation, is synthesized within the central nervous system (CNS).
• Its presence and origin in cerebrospinal fluid (CSF) have not been previously investigated.
• Understanding prothrombin's role in the CNS is crucial for neurological research.

Purpose of the Study:

• To determine the concentration of prothrombin in human CSF.
• To investigate the origin of prothrombin in CSF, differentiating between CNS production and blood-derived sources.
• To assess the impact of multiple sclerosis (MS) on CSF prothrombin levels.

Main Methods:

• Development and application of a highly specific and sensitive enzyme-linked immunosorbent assay (ELISA) for prothrombin detection.
• Paired CSF and plasma samples were analyzed from 18 healthy controls and 4 MS patients.
• Prothrombin concentrations were quantified, and CSF/plasma quotients (Q(Proth)) were calculated and compared to albumin quotients (Q(Alb)).

Main Results:

• A mean prothrombin concentration of 0.55 mg/l was found in normal CSF, compared to 121.8 mg/l in plasma.
• The mean CSF/plasma prothrombin quotient (Q(Proth)) was 4.5 x 10(-3), similar to the albumin quotient (Q(Alb) = 5.8 x 10(-3)).
• Prothrombin in normal CSF originates predominantly (>95%) from the blood, with conserved enzymatic activity.

Conclusions:

• Prothrombin in normal human CSF is primarily derived from the blood, similar to albumin.
• The concentration of prothrombin in CSF is not significantly affected by early-stage MS with minimal lesions, provided the blood-CSF barrier remains intact.
• This study establishes a baseline for CSF prothrombin levels and its origin in neurological health and disease.